Guo Gangqiang, Wang Huijing, Tong Xinya, Ye Lele, Shi Xinyu, Fang Su, Hu Ya, Han Fei, Chen Chaosheng, Ding Ning, Su Bofeng, Xue Xiangyang, Zhang Huidi
Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research & Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens & Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People's Republic of China.
Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
J Inflamm Res. 2022 Feb 4;15:775-791. doi: 10.2147/JIR.S331188. eCollection 2022.
Enhancer RNAs (eRNAs), a class of non-coding RNAs, play indispensable roles in regulating target gene transcription and maintaining cell identity in cooperation with promoters. In this study, we investigated the transcriptional landscape and potential functions of eRNAs in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).
PBMCs from five patients with stable SLE, five patients with active SLE, and ten healthy individuals (HCs) were subjected to RNA-sequencing. Putative regulators, differential expression, and pathways were analyzed. eRNAs that were significantly upregulated were first validated by RT-qPCR in 12 samples. Then, candidate eRNAs were confirmed in a validation cohort of 45 samples. We conducted comprehensive pathway analyses to explore the correlations between the candidate eRNAs and SLE pathology.
By analyzing eRNA transcript data from PBMCs from SLE patients and HCs, we identified various eRNAs and functional super-enhancers potentially related with SLE. The SLE-specificity of eRNAs seemed to be largely driven by SLE-specific transcription factors (TFs). A Venn diagram of eRNAs differentially expressed in stable, active, and total SLE vs HCs revealed that 13 and 23 eRNAs were commonly upregulated and downregulated, respectively, in patients with stable SLE and those with active SLE. The commonly upregulated eRNAs participate in regulating SLE-related pathways. Only eRNA TCONS_00034326 was significantly ( < 0.05) upregulated in PBMCs of patients with SLE when compared with those of HCs as indicated by RT-qPCR. The area under the receiver-operating curve of TCONS_00034326 for distinguishing SLE patients from HCs was 0.691. Through its putative SLE-related master TF, TCONS_00034326 is involved in multiple SLE-relevant signaling pathways, especially tumor necrosis factor signaling.
This study unraveled the transcriptional landscape of eRNAs, eRNA-related TFs, and super-enhancers in PBMCs from SLE patients and HCs. We identified a panel of SLE-relevant eRNAs, providing potential targets in SLE pathogenesis.
增强子RNA（eRNA）是一类非编码RNA，在与启动子协同调节靶基因转录和维持细胞特性方面发挥着不可或缺的作用。在本研究中，我们调查了系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）中eRNA的转录图谱及其潜在功能。
对5例稳定期SLE患者、5例活动期SLE患者和10名健康个体（HC）的PBMC进行RNA测序。分析推定的调节因子、差异表达和信号通路。首先通过RT-qPCR在12个样本中验证显著上调的eRNA。然后，在45个样本的验证队列中确认候选eRNA。我们进行了全面的信号通路分析，以探索候选eRNA与SLE病理之间的相关性。
通过分析SLE患者和HC的PBMC中的eRNA转录数据，我们鉴定了各种可能与SLE相关的eRNA和功能性超级增强子。eRNA的SLE特异性似乎在很大程度上由SLE特异性转录因子（TF）驱动。稳定期、活动期和总SLE患者与HC中差异表达的eRNA的维恩图显示，稳定期SLE患者和活动期SLE患者中分别有13个和23个eRNA通常上调和下调。这些通常上调的eRNA参与调节与SLE相关的信号通路。RT-qPCR结果显示，与HC相比，仅eRNA TCONS_00034326在SLE患者的PBMC中显著上调（<0.05）。TCONS_00034326区分SLE患者和HC的受试者工作特征曲线下面积为0.691。通过其推定的与SLE相关的主TF，TCONS_00034326参与多个与SLE相关的信号通路，尤其是肿瘤坏死因子信号通路。
本研究揭示了SLE患者和HC的PBMC中eRNA、与eRNA相关的TF和超级增强子的转录图谱。我们鉴定了一组与SLE相关的eRNA，为SLE发病机制提供了潜在靶点。
